Journal of Nutrition & Intermediary Metabolism 14 (2018) 16e21

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Journal of Nutrition & Intermediary Metabolism

journal homepage: http://www.jnimonline.com/

Nutritional supplements for the prevention of diabetes mellitus and

its complications
Sharon Yeung PharmD Candidate, Jane Soliternik PharmD Candidate,
Nissa Mazzola PharmD, CDE *
St. John's University College of Pharmacy and Health Sciences, Queens, NY, 11439, USA

a r t i c l e i n f o a b s t r a c t

Article history: Many patients commonly use nutritional supplements as an alternative or as an addition to their current
Received 13 September 2017 medication regimen to prevent or treat diseases. One of these diseases, a leading cause of death in the
Received in revised form United States, is diabetes mellitus and its complications [1]. For both type 1 and type 2 diabetes mellitus,
12 July 2018
studies have been conducted to test not only prescription medications, but also nutritional supplements
Accepted 13 July 2018
Available online 26 July 2018
that may a role in prevention of the progression of this disease and its associated complications. In this
article, we will review the efficacy of nutritional supplements that have been used for the prevention of
type 1 and type 2 diabetes mellitus and their main complications, including diabetic neuropathy, car-
diovascular disease, and retinopathy.
© 2018 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
2. Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
3. Prevention of T1DM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
3.1. Nicotinamide (B3) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
3.2. Omega-3 polyunsaturated fatty acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
4. Prevention of T2DM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
4.1. Chromium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
4.2. Magnesium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
4.3. Vitamin D . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
4.4. Fenugreek . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
4.5. Curcumin extract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
5. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Author statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

1. Introduction little or no insulin production. Some of the risk factors for devel-
opment of T1DM include family history and some suggested
Type 1 diabetes mellitus (T1DM) is an immune mediated disease environmental factors such as exposure to certain viruses and foods
characterized by destruction of pancreatic beta cells resulting in [1,2,3]. Because the body cannot produce insulin on its own, it relies
on an external source of insulin in order to be able to store glucose.
Without insulin, there are high glucose levels in the blood. If left
* Corresponding author. Clinical Health Professions College of Pharmacy and
untreated, the high levels of blood glucose can destroy nerves and
Health Sciences St. John's University, 8000 Utopia Parkway, Queens, NY, 11439, USA. blood vessels, including those in the kidneys, eyes, and the heart.
E-mail address: mazzolan@stjohns.edu (N. Mazzola).

https://doi.org/10.1016/j.jnim.2018.07.003
2352-3859/© 2018 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
 S. Yeung PharmD Candidate et al. / Journal of Nutrition & Intermediary Metabolism 14 (2018) 16e21
This can lead to complications known as diabetic neuropathy, ne-
phropathy, retinopathy, and cardiovascular disease. Kidney failure,
blindness, and increased risk of heart attack or stroke can result
without proper treatment [4]. These same complications can apply
to those with type 2 diabetes mellitus.
Type 2 diabetes mellitus (T2DM) is a progressive disease where
the body cannot make enough insulin and at the same time cells
can become resistant to insulin and are not utilize the body's in-
sulin to regulate blood sugar. It can be caused by a variety of factors
such as environmental (diet and lifestyle) and some genetic links.
There is epidemiologic data that suggest that 9 of 10 cases of T2DM
are attributed to modifiable lifestyle factors [5]. This disease is
progressive; it begins as pre-diabetes, which can be defined by the
following lab values: fasting blood sugar level ranging from 5.55 to
6.94 mmol/L and an HbA1c of 5.7e6.4% (39e46 mmol/mol) [6].
There are several supplements, which have been studied in the
prevention of T1DM, T2DM, and their complications. The following
studies looks at several natural supplements, which target different
mechanisms of prevention in patients with high risk factors for
T1DM, T2DM, and associated complications.
A study, which analyzed the Medical Expenditure Panel Survey,
found that individuals with diabetes were 1.6 times more likely to
use complementary alternative medicine (CAM) when compared to
the general population [7]. Data from a nationally representative
telephone survey showed 57% of the respondents who had diabetes
reported CAM use in the past year [8]. CAM not only limited to
nutritional supplements, though it does play a large role, but also
includes massages, acupuncture, spiritual healing, etc [9]. Due to
the willingness of patients to try CAM, it is important to look at
nutritional supplements, which may have role in prevention.
2. Methods
A PubMed search was performed using the keywords, “nutri-
tional supplements”, “diabetes”, “type 1”, “type 2”, and “preven-
tion”. Only randomized controlled studies, meta-analysis, or cohort
studies with high power were selected, and those with statistical
significance defined as p < 0.05. All studies looked at patients who
had not yet diagnosed with diabetes or had diabetes, and/or had a
goal to prevent the progression of complications. Studies that
focused on patients with risk factors for type 1 diabetes as well as
pre-diabetic patients were selected for inclusion. The articles were
reviewed by the listed authors.
3. Prevention of T1DM
3.1. Nicotinamide (B3)
One supplement, which has been investigated in the prevention
of T1DM, is nicotinamide or vitamin B3. Nicotinamide can have
protective effects on beta cells that can be helpful for those at high
risk for T1DM. One possible mechanism of action of this vitamin is
the inhibition of the DNA repair enzyme poly-ADP-ribose poly-
merase and prevention of b-cell NAD depletion [10].
Nicotinamide has been shown to have a positive effect in animal
models. In one study, which investigated non-obese rats, looked at
treatment with subcutaneous nicotinamide at a dose of 0.5 mg/g
body weight showed promising results. The rats in the treatment
arm no longer showed glycosuria and had improved glucose
tolerance [11]. This therapeutic outcome suggests that nicotin-
amide may have the same effect in humans.
In the Deutsche Nicotinamide Intervention Study (DENIS), pa-
tients that were screened as high-risk patients were randomized
into placebo or treatment groups and given slow release nicotin-
amide at a dose of 1.2 g/m2. High-risk patients were identified as
17
those who may potentially develop diabetes in the next three years
by screening patients who have siblings (age 3e12 years) which
currently have T1DM for the presence of high titer (
20 Juvenile
Diabetes Foundation units) islet cell antibodies [12]. There was no
significant delay in disease development in patients with high risk,
but nicotinamide may still be useful in patients with lower risk than
those studied here.
Another study, the European Nicotinamide Diabetes Interven-
tion Trial (ENDIT), showed similar outcomes. It was a double-blind
placebo-controlled trial of nicotinamide in 552 relatives with
confirmed islet cell antibody (ICA) levels of
20 Juvenile Diabetes
Federation units and a non-diabetic oral glucose tolerance test.
Participants were randomly assigned oral modified release nico-
tinamide (1.2 g/m2) or placebo for 5 years. Participants were eval-
uated at baseline and also received a clinical examination with
recorded height and weight, adverse events, checked biochemical
and hematological variables, and the number of returned tablets at
1 month, and 6 months after study entry and every 6 months
thereafter. Findings included 159 participants that developed dia-
betes. Of those who developed diabetes 82 were taking nicotin-
amide and 77 were on placebo. The number of serious adverse
events did not differ between treatment groups. The primary
outcome was development of diabetes, as defined by WHO criteria
[10]. Once again there was no difference in the development of
diabetes between the treatment groups.
Nicotinamide shows encouraging data in patients with recent
onset T1DM as shown in IMDIAB III study. Results showed patients
who were older than 15 years of age showed significantly higher
stimulated C-peptide secretion than placebo treated patients
(p < 0.02) [13]. C-peptide and insulin are linked when produced by
the pancreas, usually they are found in equal amounts in the body.
The more of the peptide in the blood indicates there is more insulin
to help control the body's blood glucose [14].
Nicotinamide does not show the same preventive effects in
humans as seen in animal models. There is no significant different
in the development of T1DM, however there is benefit seen in
patients who have recent onset of T1DM. For nutrition and energy
enhancement, nicotinamide is typically dosed at 2.5e5 mg daily or
every other day [15]. However, for prevention of T1DM much larger
doses were studied, up to 5 g daily, which did not show any adverse
events.
3.2. Omega-3 polyunsaturated fatty acid
Omega-3 can have insulin-sensitizing effects via increased
production and secretion of adipocytokines such as adiponectin
and leptin [16]. A potential pathway to prevention of insulin
resistance is through omega 3's anti-inflammatory effects mediated
directly or through conversion to specialized pro-resolution me-
diators such as resolvins and protectins [17e19]. Through modu-
lation of transcription factors omega 3 could also enhance fatty acid
oxidation and reduce de novo lipogenesis. These effects that could
then reduce hepatic fat accumulation and preserve hepatic insulin
sensitivity [20e23].
Omega-3 polyunsaturated fatty acid has been shown to reduce
risk of beta cell islet autoimmunity in children at risk for T1DM as
demonstrated by the Diabetes Autoimmunity Study in the Young
(DAISY). Children with increased risk were defined as those with
the HLA genotype or having a sibling or parent with T1DM. Their
omega-3 polyunsaturated fatty acid intake was measured pro-
spectively using a 111-item semi-quantitative food frequency
questionnaire (FFQ). High consumption was inversely associated
with the risk of islet autoimmunity (hazard ratio of 0.45; 95% CI,
0.21e0.96; P ¼ 0.04) [24]. It is suggested that the anti-inflammatory
properties of omega-3 polyunsaturated fatty acids can decrease the
18 S. Yeung PharmD Candidate et al. / Journal of Nutrition & Intermediary Metabolism 14 (2018) 16e21
risk of autoimmune disease.
Other benefits of omega-3 include improvement of neuropathy
in T1DM patients. A 12-month trial that investigated 40 partici-
pants with T1DM showed an increase in corneal nerve fiber length
(CNFL). Patients with T1DM and evidence of diabetic sensorimotor
polunueropath defined by a Toronto Clinical Neuropathy Score
1
were given oral 10 mL dose of seal oil u-3 PUFAs with 2330 mg of
essential fatty acids (750 mg eicosapentaenoic acid, 560 mg doco-
sapentaenoic acid, and 1020 mg docosahexaenoic acid) divided into
2 daily 5 mL doses with breakfast and dinner. Baseline CNFL was
8.3 ± 2.9 mm/mm2 and increased 29% to 10.1 ± 3.7 mm/mm2
(p ¼ 0.002) after 12 months of supplementation. However, findings
were limited by the single-arm open-label study design and small
sample size [25]. This study does not prove causality, but does show
targeted nutritional intervention can play a role in T1DM.
Diets high in omega-3 fatty acids can be helpful in this regard
and can be found in foods like salmon, mackerel, and herring [26].
Patients should try to get their daily intake from diet first before
looking into supplementation. There is no set recommended intake,
but the US Food and Drug Administration (FDA) recognizes total
intakes up to 3 g/day of EPA and DHA as generally safe [27]. Though
high doses appear to be safe they should generally be under the
guidance of a clinician. The US FDA has approved fish oil supple-
ments at a dose of 4 g/day for prescription therapy of hyper-
triglyceridemia [28]. Side effects of omega 3 supplementation
include gastrointestinal disturbances such as nausea, occurring in
approximately 4% of individuals at doses below 3 g/day and
approximately 20% of individuals at doses of 4 g/day or higher. The
most common symptom is “fishy taste” following eructation
(burping) [29].
4. Prevention of T2DM
4.1. Chromium
Chromium is a trace mineral that the body regularly needs in
small doses, however it has shown to play a role in metabolism of
lipids, proteins, and carbohydrates. Chromium is present in many
foods, especially in liver, Brewer's yeast, American cheese, wheat
germ, vegetables such as carrots, potatoes, broccoli, and spinach,
and is also present in alfalfa, brown sugar, molasses, dried beans,
nuts, seeds, mushrooms, and animal fats [30].
Often marketed to help patients with diabetes control their
blood sugars, it has also been thought to help the prevention of
T2DM. Chromium improves the action of insulin by improving
tyrosine kinase activity on the insulin receptor [31].
Analysis of the data from the National Health and Nutrition
Examination Survey (NHANES) database 1999e2010 established
that those who, in the previous 30 days, took chromium containing
supplements had a lower odds of having T2DM (OR: 0.73; 95% CI:
0.62, 0.86; P ¼ 0.001). Chromium consumptions was studied as a
dichotomous variable (did or did not take chromium). A regression
analysis was preformed with dichotomized variable at 2000 mg of
consumed chromium from supplements in 30 days. Those who
took supplements alone with no chromium did not have a change
in odds of developing T2DM [32]. Although causality could not be
determined, this data provide some evidence of chromium's role in
prevention of T2DM.
Another double blind randomized clinical trial, which studied
50 mg, and 200 mg supplementation with chromium for 3 months
did not result in any improvements in glucose homeostasis nor
anthropometry in 56 T2DM patients. Participants were evaluated
for glucose homeostasis, anthropometry and physical activity in-
tensity at baseline (day 0), day 45 and day 90 [33].
Despite promising results from previously mentioned study,
chromium proves to be ineffective. In another randomized, double
blind, placebo-controlled study that looked at 62 participants
showed no differences in fasting plasma glucose (FPG) levels. Par-
ticipants had a FPG level ranging from 5.55 to 7 mmol/L and a body
mass index
25 kg/m2. With no change to diet and physical activity,
they were allocated to receive a 4-month treatment with either
1.2 g/day of the dietary supplement or placebo; face-to-face follow-
up visits were scheduled at 2, 4 (end of treatment period) and 6
(end of study) months from randomization. They received two
capsules orally at lunchtime daily of either a dietary supplement,
containing: cinnamon, chromium and carnosine or placebo. Pri-
mary efficacy outcome was the change in FPG level at 4 months.
The dietary supplement arm showed a decreased FPG compared to
placebo (0.24 ± 0.50 vs þ0.12 ± 0.59 mmoL/L, respectively,
p ¼ 0.02). There were also no detectable significant changes in
HbA1c, insulin sensitivity markers, plasma insulin, plasma lipids
and inflammatory markers [34]. Weaknesses include small sample
size and also the dietary supplement was not purely chromium
alone, therefore no significant conclusions can be drawn.
Causality between chromium and the prevention of T2DM could
not be proved by of the studies mentioned above, therefore chro-
mium cannot be said to help the prevention of T2DM. There were
also several studies, Guimara ~es e al. and Liu et al., which also
showed no differences in chromium arm and placebo arm. Rec-
ommended dietary doses for chromium are 25 mg for women and
35 mg for healthy men [35]. Acceptable chromium intake is
30e40 mg/day in order to achieve the daily requirements and that
healthy people usually can reach in their customary diet [36]. Long-
term effects of supplementation have not been well studied.
Although the toxicity of chromium is low, high doses of chromium
have been related to chromosomal damage [37]. Some cases related
to renal and hepatic toxicity, rhabdomyolysis, and psychiatric dis-
turbances [38]. Thus, the use of chromium for long periods may
result in a toxic risk.
4.2. Magnesium
Magnesium is an essential cofactor of high-energy phosphate-
bound enzymatic pathways involved in the energetic metabolism,
synthesis of protein, and modulation of glucose transport across
cell membranes [39]. Low magnesium levels are associated with an
increased risk of developing metabolic syndrome [40]. One pro-
posed mechanism involves the shift of intracellular magnesium.
Insulin is involved with the shift of magnesium intracellularly, in
turn, intracellular magnesium seems to regulate insulin activity on
oxidative glucose metabolism. Low intracellular magnesium causes
disorders in tyrosine kinase activity at the insulin receptor level,
which results in decreased insulin sensitivity and insulin-mediated
glucose uptake [41,42].
A meta-analysis of 13 prospective cohort studies with over
500,000 participants, showed evidence that magnesium intake is
inversely associated with risk of T2DM in a dose-related manner
(Relative Risk 0.78, 95% CI, 0.73e0.84). The RR of T2DM for every
100 mg/day increment in magnesium intake was 0.86 (95% CI
0.82e0.89) [43].
The Iowa Women's Healthy Study, a cohort of postmenopausal
women, showed a significant reduction in the relative risk of dia-
betes, in women with increased intake of whole grains and other
food sources of magnesium. During 6 year of follow-up, 1141 inci-
dent cases out of total of 35,988 of diabetes were reported. Using a
127-item food-frequency questionnaire, magnesium remained
significantly and inversely related to T2DM [44]. This data supports
the protective role that magnesium plays in prevention, however
cohort studies are weaker than randomized clinical trials so no
strong conclusion can be made from the Iowa Women's Health
 S. Yeung PharmD Candidate et al. / Journal of Nutrition & Intermediary Metabolism 14 (2018) 16e21
study in regard to magnesium.
The studies that were discussed only looked at dietary intake
of magnesium and not direct supplementation of magnesium.
Though dietary intake shows and inverse relationship related to
the development of T2DM, it cannot be said that magnesium itself
can prevent the development of T2DM. Magnesium can be found
in many natural foods as well as fortified foods. It can be found in
nuts, whole grains, green leafy vegetables, and legumes [38],
therefore the inverse relationship can be contributed to other
vitamins and minerals found from these foods. Magnesium is
relatively non-toxic in those people with conserved renal func-
tion. Renal insufficiency increases the likelihood of toxicity due to
hypermagnesemia [45]. Oral magnesium is safe when used in
doses below the tolerable upper intake level of 350 mg daily
where as doses greater than 350 mg frequently cause loose stools
and diarrhea [46].
4.3. Vitamin D
Vitamin D helps the body maintain the correct blood calcium
levels and blood phosphate levels, as well as prevention of rickets
and osteomalacia [47]. Healthy sources of vitamin D are salmon,
mackerel, tuna, as well as fortified milk [48]. It may play func-
tional role on glucose tolerance through its effects on insulin
secretion and insulin sensitivity. By reducing the risk of insulin
resistance, a common precursor to T2DM, it may help prevent
T2DM [49].
In a 29 year follow up of over 9000 patients from Copenhagen
City Heart Study shows that low levels of vitamin D can increase
the risk of developing metabolic syndrome or insulin resistance
[50]. Vitamin D levels were categorized as
20 mg/L [
50 nmoL/
L] (sufficient), 10e19.9 mg/L [25e49.9 nmoL/L] (insufficient),
5e9.9 mg/L [12.5e24.9 nmoL/L] (deficient), and <5 mg/L
[<12.5 nmoL/L] (severely deficient). Upon analysis, a multivari-
able adjusted hazard ratios found that development of T2DM
increased with decreasing concentrations of 25(OH)D. For
25(OH)D < 5 mg/L (<12.5 nmoL/L) the HR was 1.22 (95% CI
0.85e1.74) when compared to
20 mg/L. Another study that
looked at 2465 Caucasian men and women, subjects having 25-
OHD3 levels
80 nmol/l were half as likely to have diabetes
compared to individuals with levels <37 nmol/l [51].
A large prospective study 83,779 women, with no history of
diabetes, were followed for 20 years. Results showed a daily intake
of >800 IU of vitamin D and >1200 mg of calcium supplements
were inversely related to the incidence of T2DM when compared to
an intake of <400 IU of vitamin D and <600 mg of calcium [52]. At
smaller doses than previously mentioned a second large-scale trial
was conducted. Among 33,951 healthy postmenopausal women
over a period of 7 years showed no difference in incidence of dia-
betes. They consumed
400 IU of vitamin D3 daily as well as
1000 mg/day of calcium [53].
Regular supplementation recommendations of vitamin D de-
pends on the patient's current blood levels, healthy range of 25(OH)
D is > 20 ng/L (50 nmoL/L) [54]. Doses of vitamin D for the pre-
vention of T2DM are not established nor can it be recommended,
but large doses >800IU have shown some improvement. Over all
the Institute of Medicine suggests vitamin D for the following age
ranges: 1e70 years of age, 600 IU daily; 71 years and older, 800 IU
daily; pregnant and lactating women, 600 IU daily [55]. Vitamin D
toxicity can present with symptoms of hypercalcemia such as
nausea, dehydration, constipation, polyuria and kidney stones.
Though vitamin D excess can cause hypercalcemia, it is very rare
and would only be seen after ingestion of >10,000 IU/day of
vitamin D. Levels of 80 ng/ml of 25(OH)D has been the lowest re-
ported level associated with toxicity [54].
19
4.4. Fenugreek
Fenugreek has a role in glucose homeostasis, which can be
helpful in pre-diabetic patients. One possible mechanism is by
improving insulin sensitivity and decreasing insulin resistance as
well as of reducing glucose absorption [56].
In a 3-year randomized, controlled, parallel study, patients with
pre-diabetes saw significant reduction in fasting plasma glucose
(5.76 ± 0.53 vs 5.53 ± 0.31 mmoL/L; p < 0.05) as well as reduction in
postprandial plasma glucose (7.93 ± 1.48 vs. 7.16 ± 1.64 mmoL/L;
p < 0.01). Participants took 10 g/day of fenugreek. Supplementation
with fenugreek also showed benefit in reducing low-density lipo-
protein cholesterol (6.53 ± 1.46 vs. 5.60 ± 1.33 mmoL/L; p < 0.05).
Study subjects and matched-controls were selected and monitored
once every 3 months. Height, weight, BMI, waist-to-hip ratio, FPG,
post prandial plasma glucose, lipid profile - serum cholesterol,
serum triglycerides, high density lipoprotein cholesterol, low
density lipoprotein cholesterol and serum insulin were recorded at
baseline and during follow-up visits. Those in the control group
who did not receive fenugreek had a 4.2 times greater chance of
developing diabetes [57].
Twenty-five newly diagnosed patients with T2DM (fasting
glucose < 11.1 mmol/L) were randomly divided into two groups.
Group I (n ¼ 12) received 1 gm/day hydroalcoholic extract of
fenugreek seeds and Group II (n ¼ 13) received usual care (dietary
control, exercise) and placebo capsules for two months. Results
showed no differences in fasting blood glucose and 2 h post pran-
dial blood glucose. However, area under curve of blood glucose
(2375 ± 574 vs 27,597 ± 274) as well as insulin (2492 ± 2536 vs.
5631 ± 2428) was significantly lower (p < 0.001)56. Patients with
recent and mild T2DM may see benefit with fenugreek glycemic
control.
Some side effects of fenugreek are gastrointestinal symptoms
such as diarrhea, stomach upset, bloating, and gas [58,59]. Doses of
25 g/day of fenugreek seeds were found to be safe [60]. It is also
important to note there are several drug interactions with fenu-
greek including interactions with anticoagulants, warfarin [61], and
some antidiabetic drugs [62,63].
4.5. Curcumin extract
Turmeric, derived from the plant Curcuma longa, is a gold-
colored spice commonly used in the Indian subcontinent, not
only for health care but also for the preservation of food and as a
yellow dye for textiles. Curcumin is the main component of
turmeric that gives it its yellow coloring [64]. Curcumin modulates
various signaling molecules, including inflammatory molecules,
transcription factors, enzymes, and protein kinases. This modu-
lating activity can play a role in its anti-inflammatory properties
[65].
Curcumin shows positive evidence in improving beta cell
function. In a randomized, double-blinded, placebo-controlled trial
with 240 patients with pre-diabetes, there were no patients in the
curcumin treated group that developed T2DM compared to 16.4% in
the placebo group who went on to develop T2DM. Pre-diabetic
patients to be included in this study had to fall into at least one
of the following criteria: fasting plasma glucose 55.5e6.88 mmol/L
(indicating impaired fasting glucose), an oral glucose tolerance test
plasma glucose at 2-h post glucose load 7.77e11.04 mmol/L (indi-
cating impaired glucose tolerance), and HbA1c range from 5.7% to
6.4% (39e46 mmoL/mol). Diagnosis of prediabetes was later veri-
fied a second repeating test of all of the above-listed criteria on a
different day. The treatment arm was given 6 capsules (250 mg of
curcumin/capsule) with directions of take 3 capsules twice daily.
After the 9-month treatment intervention, it can be demonstrated
20 S. Yeung PharmD Candidate et al. / Journal of Nutrition & Intermediary Metabolism 14 (2018) 16e21
the curcumin in a patient with pre diabetes can be beneficial [66].
Curcumin also shows positive effects in patients who have
already developed T2DM. A randomized double-blind placebo-
controlled trial, 118 subjects with T2DM were randomized to cur-
cuminoids (1000 mg/day co-administered with piperine 10 mg/
day) or matching placebo for a period of 8 weeks. Serum total
antioxidant capacity, superoxide dismutase (SOD) activities and
malondialdehyde (MDA) concentrations were measured at baseline
and after the supplementation period. Curcuminoids supplemen-
tation caused a significant elevation in serum total antioxidant
capacity (p < 0.001) and SOD activities (p < 0.001), while serum
MDA levels were significantly reduced compared with the placebo
group (p < 0.001). These results remained statistically significant
after adjustment for potential confounders (baseline differences in
body mass index and fasting serum insulin) [67]. Curcumin shows
antioxidant effect but still needs further studies determine the
impact on the prevention of T2DM.
One of the major setbacks with curcumin is its poor bioavail-
ability [68]. A 500 mg curcumin regimen administered 3 times daily
to T2DM nephropathy patients in a 2-month randomized, double-
blind, and placebo-controlled study improved urinary protein
excretion and expression of transforming growth factor and inter-
leukin (IL)-8 [69]. High doses of curcumin have shown to have
adverse effects including nausea, diarrhea, increased liver function
tests, and increased risk of bleeding [70].
5. Conclusion
Since diabetes is a disease that touches the lives of millions
nationally, it is important to recognize the significance of preven-
tion. Although there are many supplements that are marketed for
not only the treatment, but also the prevention of diabetes and its
complications, there are still many concerns to CAM use. Dietary
supplements specifically can be associated with adverse effects,
drug interactions, and contamination of products. Therefore, mak-
ing it the utmost of importance for patients to report all drugs they
are taking, including supplements, to the their doctors and phar-
macist so that the best care plan can be made for them. As dis-
cussed, there are several promising nutritional supplements, which
can have a preventive role in the development of diabetes and its
complications. Many have shown promising results and others
have failed to demonstrate effectiveness. Aside from these sup-
plements, the best recommendation and suggestion for prevention
of diabetes, especially T2DM, is diet and physical activity.
Author statement
Sharon Yeung, Author 70%.
Jane Solitnerik Author 10%.
Nissa Mazzola, Author 10%, Editor.
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