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Nonvitamin, Nonmineral Dietary Supplementation in HIV-Positive People

Mara R. Sansevero, MS, RD, LDN, CDE^*,
Robert Houser
Grace Phelan
Christine Wanke
Alice Tang
Kristy Hendricks^,,

^* Cambridge Health Alliance at Cambridge Hospital, Cambridge, Massachusetts; Tufts New England Medical Center, Frances Stern Nutrition Center, Boston, Massachusetts; Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts; and the Department of Public Health and Family Medicine, Tufts University School of Medicine, Boston, Massachusetts

Correspondence: Correspondence: Mara R Sansevero, MS, RD, LDN, CDE, Cambridge Health Alliance-TCH-PCU, 1493 Cambridge Street, Cambridge, MA 02139. Electronic mail may be sent to MRSansevero{at}hotmail.com.

Background: Many consumers with chronic diseases attempt to take control of their health by using dietary supplements. The objective of this study was to describe current nonvitamin, nonmineral (NVNM) supplement use of HIV-infected persons in the Nutrition for Healthy Living (NFHL) cohort, the financial burden that buying these supplements might pose to this population, and to review current literature on potential interactions between NVNM supplements. Methods: At baseline visit, participants were educated by a registered dietitian on keeping a complete 3-day food record (including all supplements) for 2 weekdays and 1 weekend day. Seventy-two subjects reported consumption of NVNM supplements, and their food records were reviewed in detail. Results: Each of the 72 subjects in this study used a mean of 6 NVNM supplements, which may have been in the form of a pill, powder, bar, or liquid. The 6 most common were glutamine (51%), N-acetyl-cysteine (36%), fish oil (33%), -lipoic acid (32%), acetyl-L-carnitine (28%), and coenzyme Q10 (28%). Participants were also taking an average of 4 vitamin/mineral supplements; the 6 most common were multivitamin/multimineral (83%), vitamin E (51%), vitamin C (47%), vitamin B complex (43%), calcium (29%), and selenium (28%). Conclusions: With a total of 107 different types of NVNM supplements, our estimated cost examples indicated a weekly supplement regimen cost of between $25 and $40 dollars. According to literature review, taking an NVNM supplement may involve some risk because many components have not been studied and these products are not tightly regulated.

The use of dietary supplements as a part of healthcare has become more common for many people. Many consumers are attempting to take control of their health, buying supplements without the recommendation of their healthcare providers. From supermarket shelves to online distributors, there are >29,000 types of supplements from which to choose, and it is estimated that consumers spend over $17 billion a year on these products.^1,2

The use of dietary supplements is reported to be higher in individuals who have chronic diseases or other self-reported medical conditions.³ Several studies report that people infected with human immunodeficiency virus (HIV) use supplements at a higher rate than the general population.^4,5 Within the category of dietary supplements is a group of nonvitamin/nonmineral (NVNM) supplements, which includes herbs or other botanicals, concentrates, metabolites, constituents, and extracts. In 1 study, 32% of adults were found to be taking at least 1 of these supplements, the most common being echinacea and gingko biloba.² Of HIV-infected people in a national sample, approximately 15% used herbal medicine.⁶ As NVNM supplement use becomes more popular and new supplements are put on the market, questions arise about how the components of these pills will interact with conventional medicine and alter patient care. Also of concern is how the financial burden of these supplements will affect the patient.

Health maintenance for people living with HIV and acquired immunodeficiency syndrome (AIDS) relies heavily on control of viral replication by highly active antiretroviral therapy (HAART). Therefore, it is important to know if supplements interfere with HAART metabolism. It is also important to know what supplements the HIV-infected population is taking so that further research may be done on these specific compounds and the interaction with HIV medications and disease process.

The objective of this study was to describe current NVNM supplement use of HIV-infected people and the financial burden that buying these supplements might pose to this population, as well as reviewing the current literature on potential interactions between NVNM supplements.

	Methods

Top Methods Results Discussion Conclusions

 
Data for this study were taken from the Nutrition for Healthy Living (NFHL) study, a longitudinal investigation of the nutrition and metabolic consequences of HIV infection. The Tufts–New England Medical Center Institutional Review Board reviewed this study and participant confidentiality was ensured. Details about the cohort have been published elsewhere.⁷

Subjects
Subjects from the greater Boston area or Rhode Island were enrolled between 1995 and 2002. Inclusion criteria were documented HIV infection and age >18 years. Individuals were excluded if they were pregnant or had diabetes, thyroid disease, malignancies other than those associated with HIV, or inadequate fluency in English at the time of enrollment.

Data Collection
Participants came for semiannual visits at the study clinic, where medical, nutrition, dietary intake, body composition, and quality-of-life data were collected. At the first baseline NFHL visit, participants met with a registered dietitian and were educated on keeping a complete 3-day food record (including all ingested supplements) for 2 weekdays and 1 weekend day. Before subsequent follow-up appointments, which took place every 6 months, 3-day food record forms were mailed to participants. Food records were analyzed using the Nutrition Data System (NDS) software, developed by the Nutrition Coordinating Center, University of Minnesota, version 2.92, though analysis did not include NVNM supplements because this information is not generally available from product analysis, is not standardized, and may be incomplete.

Study Design
This study was a cross-sectional, descriptive analysis evaluating current usage of dietary supplements in HIV-infected patients enrolled in the NFHL study. Subjects were seen in our study clinic between September 1, 2001, and September 1, 2002. Only data from their most recent visit were used. Subjects were excluded if they had not completed a 3-day food record within the specified time frame or if the food record was marked unreliable (36 subjects). After exclusions, data from 368 subjects were used in this study. Of the 368 subjects, those reporting consumption of NVNM supplements (such as herbs or botanicals) are the focus of this report (n = 72). Because NDS does not include NVNM supplements, subjects who reported NVNM ingestion had their food records reviewed in detail by hand for the calculation of NVNM use. We also looked at the number of vitamin/mineral (VM) supplements these subjects were taking.

Statistical Analysis
Simple frequencies, averages, and percentages about demographic characteristics and NVNM supplement intake were calculated. A price list of the supplements taken by NVNM group subjects was assembled in 2005. Because there is not a single source for supplement prices, several sources were used. As subjects in this study were from the greater Boston area, the Boston Buyers Club (BBC) was used as a resource to estimate prices paid for supplements. Supplements of the same type and dose were grouped together and the same price used. These include protein bars, enteral products, and multivitamin/minerals. If the supplement was not found at BBC, it was researched at Drugstore.com, and the first supplement that matched the description was used. For all other supplements, an online search engine was accessed, and the first supplement that matched the description was used. Some subjects wrote the doses and the brand names of the supplements they took, whereas others did not. In cases where no specifications were included, we assumed it was similar to what other subjects were taking and based the prices on this assumption. If after extensive searching we could not find a matching dose for a given supplement, we chose a supplement with a dose comparable to what other subjects were using most commonly. This was done over the course of the year after the study was completed.

	Results

Top Methods Results Discussion Conclusions

 
The demographic characteristics of individuals using NVNM supplements compared with the entire cohort are shown in Table 1; 24% of men used NVNM supplements and 8% of women used NVNM supplements. Male NVNM users were predominantly Caucasian (82%). Compared with the overall cohort, a greater percentage of the men who used NVNM were educated with at least a high school diploma (95%), lived above the poverty line (74%) in secure housing (96%), and contracted HIV via male-to-male sex (90%). Women who used NVNM were Caucasian (100%) as compared with the cohort, in which the majority of women were African Americans (44%). The female NVNM users compared with the overall group had a higher education level, with at least a high school diploma (100%); lived above the poverty line (80%); and had secure housing (100%).

Each of the 72 subjects in this study was taking a mean of 6 NVNM supplements, which may have been in the form of a pill, powder, bar, or liquid. There were a total of 107 different types of NVNM supplements used, which participants were taking either as single elements or in combination with vitamin and minerals, or as additives to macronutrients. As shown in Table 2, the 6 most common NVNM supplements were glutamine (51%), N-acetyl-cysteine (NAC; 36%), fish oil (33%), -lipoic acid (ALA; 32%), acetyl-L-carnitine (ALC; 28%), and coenzyme Q10 (28%). In addition to NVNM and VM supplements, many participants were taking protein and enteral supplements. Protein bars were consumed by 25% of the participants, whereas liquid enteral supplements were consumed by 14%.

In addition to taking NVNM supplements, participants were taking an average of 4 VM supplements. The 6 most common VM supplements taken (Table 3) were a multivitamin/multimineral (83%), vitamin E (51%), vitamin C (47%), vitamin B complex (43%), calcium (29%), and selenium (28%).

The cost of supplement regimens varied widely. Some participants were taking many single component supplements, whereas others were taking 1 or 2 combination pills with as many as 35 different NVNM components; some patients listed brand names, whereas others did not. In addition, the participants' supplement regimens on a weekly basis were highly varied. Due to this variability, we investigated in more detail 6 participants taking the most single-element NVNM supplements, all of whom were men.

Case Examples
As examples, we have included tables for the supplement intake of each of these 6 participants (Table 4). All were white men between the ages of 42 and 62. The first was taking 10 different NVNM supplements and 7 vitamin and minerals and consumed protein bars with alternative additives and protein shakes, as well as liquid amino acids. The estimated cost for his reported intake of supplements was $36.30 weekly, or $1887.60 annually.

The next case was taking 6 different NVNM supplements, 6 VM supplements, and consumed protein powder shakes with alternative additives. The estimated cost for his reported intake of supplements was $35.90 weekly, or $1866.80 annually.

Example 3 was taking 16 different NVNM supplements, 3 VM supplements, and consumed enteral supplements. The estimated cost for his reported intake of supplements was $34.34 weekly, or $1785.68 annually.

Example 4 was a 50-year-old white man. He was taking 10 different NVNM supplements, 6 VM supplements, and consumed protein shakes with NVNM additives and enteral supplements. The estimated cost for his supplements was $38.75 weekly, or $2015.00 annually.

Example 5 took 11 different NVNM supplements and 1 mineral supplement and consumed energy shakes with NVNM additives, enteral supplements, and liquid creatine. The estimated cost for his reported intake of supplements was $25.63 weekly, or $1332.76 annually.

The sixth example was taking 17 different NVNM supplements and 11 VM supplements. The estimated cost for his reported intake of supplements was $40.29 weekly, or $2095.08 annually.

	Discussion

Top Methods Results Discussion Conclusions

 
In this study, we found that participants who used NVNM supplements were taking an average of 4 VM supplements and 6 NVNM supplements. Compared with those who did not take supplements, those who took NVNM supplements were more likely to be white and well-educated, had higher incomes and secure housing, were not IV drug users, and were more likely to be receiving appropriate HIV/AIDS therapy. In a previous paper about this study, the diet of these individuals was found to include higher amounts of fiber and protein compared with subjects not taking NVNM supplements.⁷ Also, participants who took NVNM consumed more calories from polyunsaturated and monounsaturated fatty acids than other groups (nonsupplement users, VM users, enteral supplement users) and fewer calories from saturated and trans-fatty acids.⁷ NVNM supplements taken by >25% of users were L-glutamine, NAC, fish oil, ALA, acetyl-L-carnitine, and coenzyme Q_10.

Glutamine was the NVNM supplement taken by the highest number of individuals, with 51% reporting consumption of some form of the nutrient. Glutamine is an abundant amino acid in the body and is stored in the skeletal muscle of the body. Deficiencies can develop when the immune system is compromised. One randomized, double-blind, controlled trial demonstrated that glutamine supplementation increased body weight, body cell mass, and intracellular water and could provide a highly cost-effective therapy for the rehabilitation of HIV-positive patients with weight loss.⁸ L-Glutamine has also been shown to help reduce diarrhea in participants with HIV who are receiving HAART.⁹

NAC was taken by 36% of the NVNM users. NAC is a glutathione (GSH) precursor and a sulfur-containing amino acid. It is postulated that NAC supplementation can restore cysteine and GSH levels and inhibit the replication of the HIV virus. Studies have shown that reduced GSH and cysteine levels are associated with increasing viral load.^10,11 One study found that cysteine deficiency contributes to impaired immunological function in HIV patients and that NAC treatment may be recommended for patients to assist immune function.¹²

Fish oil was taken by 23 subjects, 33% of all NVNM users. -3 Fish oil, also called marine oil, contains eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are polyunsaturated fatty acids. Patients living with HIV infection, with or without HAART, often have high serum triglyceride levels and low levels of high-density lipoproteins. Fish oils may be useful in lowering triglyceride levels, including individuals living with HIV. One study showed that although serum triglycerides were reduced with -3 fatty acid supplementation, low-density lipoprotein cholesterol levels increased, so the effect of -3 fatty acid supplementation is still unclear.¹³ Another important indication for fish oil supplementation may be to decrease mortality in those who have had myocardial infarctions. Fish oils may also be indicated for lowering blood pressure and for alleviating some of the symptoms of rheumatoid arthritis.^14,15 It has been shown that individuals with heart disease may reduce their risk of sudden cardiac death by taking -3 fatty acids at 1 g per day,¹⁶ but it has not been studied in HIV-positive patients.

ALA was taken by 32% of the NVNM users (23 people). ALA is also known as thioctic acid and is a vitamin-like antioxidant. It is not an essential nutrient because it is made in small amounts in the body. ALA has been used in treatment of diabetic polyneuropathy.¹⁷ It is postulated that ALA may be able to inhibit the replication of HIV, though more research is needed.^18,19

ALC was taken by 28% of NVNM users in this study. ALC is a compound that transports long-chain fatty acids across the inner mitochondrial membrane in the form of acetyl carnitine. One study demonstrated that serum ALC levels are decreased in neuropathy associated with nucleoside reverse transcriptase inhibitor (NRTI) therapy. ALC promotes energy metabolism and may promote regeneration of nerves, as well as lead to symptom relief. ALC treatment improved symptoms, led to peripheral nerve regeneration, and was proposed as a pathogenesis-based treatment for distal neuropathy.²⁰ Another study showed that ALC may prevent cell death of CD4 cells.²¹

Coenzyme Q10 was taken by 20 persons, or 28% of the NVNM users. This vitaminlike fat-soluble substance is also known as ubiquinone, a compound made naturally in the body and acting as an antioxidant. High concentrations can be found in the heart's muscle, the liver, and the gums. Coenzyme Q10 is used by cells to produce energy needed for cell growth and maintenance and is also used by the body as an antioxidant. This compound has a wide range of properties, making it potentially useful in many types of ailments. It has been studied in relation to Parkinson's disease, mitochondrial abnormalities, migraines, congestive heart failure, hypertension, and diabetes mellitus. Research is ongoing to determine any benefit in individuals infected with HIV/AIDS.²²

Although the abovementioned NVNM supplements were taken the most often by our subjects, there were many other supplements taken in smaller amounts. Milk thistle was used by 18 people in this study. Milk thistle is postulated to help protect the liver in patients with toxic hepatitis, fatty liver, cirrhosis, ischemic injury, and viral liver disease.^23,24

There are many concerns about consumption of NVNM products, and further research is necessary. Patients buying and taking these products may be at risk of receiving little to no benefit, with the potential for harm at a considerable expense to themselves. A study showed a large reduction in indinavir concentrations with patients taking St. Johns wort.²⁵ One observational study has suggested that ma huang, guarana, ginseng, and St John's wort were associated with frequent negative events.²⁶ HIV-infected patients frequently use St John's wort, echinacea, and garlic; these supplements have been shown to interact with medications.²⁷ Kava has been found to possibly cause hepatic toxicity.²⁸ Commonly used herbal medicinals associated with drug-herb interactions were listed in a scientific study in 1998²⁹; the list included garlic, ginger, ginkgo, ginseng, saw palmetto, and valerian, which were taken by our subjects in this study. Other concerns of NVNM users include that herbs and mixtures can vary from manufacturer to manufacturer and potency of various ingredients may be affected by conditions of storage, handling, and preparation. It has also been reported that labels may be incorrect or that the wrong part of the plant may have been harvested.³⁰ A recent national survey reporting adverse events from taking various supplements showed that the most common symptoms were heart/chest problems, abdominal pain, headache, rash, and allergy/reaction. When subjects were asked about taking other medications or using dietary supplements instead of prescriptions, more supplement users who reported adverse events reported taking supplements while taking a prescription drug than supplement users who did not report adverse events. Also, more supplement users who reported adverse events consumed a supplement instead of a prescription drug to treat or prevent a health problem than users who did not report adverse events.³¹

	Conclusions

Top Methods Results Discussion Conclusions

 
NVNM supplement use is common in selected individuals living with HIV infection. On average, our subjects were taking 6 NVNM supplements and 4 VM supplements. Our estimated cost examples indicated a weekly supplement regimen of between $25 and $40 dollars. Taking an NVNM supplement may involve some risk because many components have not been studied and these products are not tightly regulated. Questions remain about individual components' bioavailability of source ingredient, extraction and processing procedures, as well as any interactions caused by active constituents with diet or medications. Cost estimates were obtained according to figures obtained during 2005; thus, these figures may slightly underestimate current costs due to inflation.

1 Marcason W. What are some resources that can help my clients sort through conflicting information in dietary supplements? J Amer Diet Assoc. 2003;103:712 –713.

Nutrition in Clinical Practice, Vol. 22, No. 6, 679-687 (2007)
DOI: 10.1177/0115426507022006679


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Sansevero, M. R. Articles by Hendricks, K. Search for Related Content PubMed PubMed Citation Articles by Sansevero, M. R. Articles by Hendricks, K. Pubmed/NCBI databases Medline Plus Health Information Dietary Supplements Social Bookmarking                         What's this?