# Presentation: 211748

## Dietary Supplements Database Update

- Johanna T Dwyer, D.Sc.
- Office of Dietary Supplements
- NIH

## Rationale

- Dietary supplement exposure is high: >50%
- $18 billion/yr
- Public health impact unknown
- Tools to validly document and quantify intakes lacking

- DSID

**Notes:**
A recent report of the USDHHS Inspector Generl found that 70% of the US population had tried suppelemnts. 

## Needed to quantify exposure/public health impact of dietary supplements:

- Validated/standardized instruments to collect data
**Composition of dietary supplements**
- Validated tools to analyze data
- Validated approaches to merge with dietary intakes to obtain total intakes

- DSID

## Need for DSID

**Accurate measurement of intakes and exposures requires:**
**Databases of DS labels (NCHS/CDC) and ingredients (USDA)**
**Methods and reference materials program**
**DS databases *****not***** yet *****based on analytical data***
**Amounts of ingredients in DS unknown except for label claims**

- DSID

## Ultimate Goal for Dietary Supplement Databases

** ****Use improved databases to research role of dietary supplements in**
-  optimal physical and mental health
-  disease prevention, risk factor reduction
-  effects on biological systems, and physiological impact across life cycle
**Make available to public**
**Reach out and inform public**

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## Slide 6

- DSID

**ODS Dietary Supplement Ingredient Databases  DSID**
**Label databases**
**NHANES  label database**
**NHANES-ODS**
**Industry foundation label database pilot: now readying SOW for a procurement **
**Analytically verified database**
**ARS-ODS dietary supplement ingredient database**

- DSID

## Progress in Dietary Supplement Data Base Development

**Use to research role of dietary supplements on health**

**Label databases**
**  ****NHANES**
**              ****at NCHS**
**Industry foundation**
**Congressionally requested**

**Information to**
**public**

**Analytically Validated**
**Dietary Supplement**
**Ingredient Database (DSID)**** **
**at ARS/USDA**

- DSID

## Dietary Supplement Database

**Preliminary work:**
- ODS workshops with other Federal agencies, academic researchers, and the private sector
- Outcome: DS ingredient database needed & feasible
**Published in J Nutrition 133: 573S-634S 2003**
**J. Food Comp.Analysisi 17; 493-500 2004**
**J. Food Comp****. Analysis 18: in press**
**Need is there****:**
- Much NIH and other research involves DS
- Total intakes of nutrients and DS exposures depend on accurate measures of DS intake, since intakes so high for some groups
- Some evidence of drug-DS interactions

- DSID

## 1. Dietary Supplement Ingredient Database

** ****Immediate Goals****: **
**Improve methods by linking dietary supplement label declarations in Supplement Facts box for products used in  NHANES with data on composition from *****validated chemical analyses***
***Prioritized ******analyses based on exposure (from NHANES 1999-2000), validity of methods, availability of reference materials, NIH and other  agency interest***
***Nutrients & other constituents of public health concern first priority***
*vitamins A, B-6, B-12,C,D,E & folic acid/folate*
*Minerals: calcium, iron, magnesium, potassium, selenium, sodium, zinc*
*Other: beta carotene, omega 3’s (EPA,DHA,ALA) , caffeine (FDA)*
**Partners:**
**	****Agricultural Research Service, USDA**
**	****NIST inDOC**
**	****FDA for caffeine**

- DSID

## 1.DSID Dietary Supplement Ingredient Database

**Today**
**Implementing plan for collection of analytical information on DS ingredients using ARS contractors**
**In Process:**
**Focus first on **
**multivitamin-mineral supplements, antacids, vitamins E,C, B  calcium,  other single mineral supplements & caffeine**
**Pilot with labs analyzing reference materials completed completion****.**
- Future:
**Implement sampling plan to collect DS and complete analyses **
**Integrate data with NHANES label-based data base**
**Tackle other  high public health priority nutrients and botanicals**

- DSID

## 2.NHANES Dietary Supplement Label Database

**Goals:**
**Provide information on selected ingredients declared in Supplement Facts labels for dietary supplements used in NHANES (mostly nutrients)**
**Make information publicly available**
**Facilitate analysis of total nutrient intakes (food plus dietary supplements)  in NHANES and other research**
**Partners:**
**	****	****NHANES/NCHS/CDC/USDHHS**
**	****	**** **

- DSID

## 2.NHANES label-based DS database

**Today:**
**DS frequency  of use in NHANES and label informatin available to public on web at NHANES website**
**In process**:
**Document DS intakes in NHANES**
**Total intakes of nutrients,  frequency of consumption, dose, etc.**
**Update values for products now on the market **
**Make label database more user friendly**
**Future**:
**Better estimates of total nutrient intake **
**More analytical substantiation of DS label values**
**Botanicals of high public health interest**
**Examine possibilities for integrating with universal label database**

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## 3. Nationwide Dietary Supplement Label Database

** ****Congressional Language:**
** *****“ ******The committee ..expects ODS to contract with ******industry non-profit associations or foundations****** which currently have and maintain a database of dietary supplement labels to develop, create, continually update, maintain and make available to government and research entities a database of all supplement labels sold in the United States. The creation of this database would allow ODS to have access for research purposes to all known supplements manufactured in the United States and to allow access by other Federal agencies for ensuring safety to consumers, through the mandatory listing of ingredients in these products on the label, who purchase supplements manufactured and /or sold in the US “***
**Pg 170 Committee Report NIH Appropriations 2005-6 Senate**

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## 3.Nationwide Dietary Supplement Label Database

** ****Immediate Goals****: **
**Test the feasibility of developing a dietary supplement label database of all DS marketed in the USA**
**Build on labels already collected by a private industry foundation sponsored by National Nutritional Foods Association  and the NHANES label database**
**1 yr pilot: **
**Focus on nutrients, research uses in pilot**
**Partners:  Not yet determined**
**	****Sole source issued and responded to by RTI NNFA , after two federal panel technical reviews procurement was not made**
**	****SOW and RFP under consideration by ODS for full and open competition and contract for publicly available database**

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## 3.Nationwide Dietary Supplement Label Database

**Today:**
**Congressional language 2004**
**concept approved by NCAAM Council 1/05 ,**
**sole source approved,  SOW , RFP issued 6/05; review 8/05 failed**
** ****reissued as pilot 09/05, review 10/05 for pilot failed**
** ****now reconsidering SOW and seeking partners; full and open competition sought**
**In process****:**
**Federal Tech Review of sole source NNFA pilot application 10/05**
**Next steps await review**
**Future**:
**Complete information on nutrients & other DS ingredients sold/marketed in USA**
** ****Publicly available, free**
**More user-friendly source of information**
**Better exposure assessment **

- DSID

## Databases all sides of the same coin

-  **NHANES label-based DS database**
**DS label values for nutrients in products reported by NHANES participants 1999-2000**
**Database of all DS labels**

**DSID Dietary Supplement Ingredient Database**

***Analytically validated***
*** ******DSID***

**DS label values for **
**nutrients, other ingredients, **
**claims, etc. for all products sold in USA**

- DSID

## Related Projects 

**Today:**
**Motivations for DS use completed & papers started**
**Supplements to U Hawaii for validity reliability DS use studies**
**Supplement to U Minnesota to develop DS software**
**Meetings with many gvt groups on structured vocabularies**
**In process**:
**Consider incorporating revised questions on DS use in HNIS, NHANES**
**Publish data on DS motivations for DS use**
**Future**:
**Incorporate valid and reliable questions on DS use into HNIS, NHANES other federal population based surveys**
**Develop user friendly system for categorizing and naming DS**
**Develop tools for public that are valid, reliable and user-friendly for better exposure assessment **

- DSID

## ODS Objective: Quantify intakes of nutrients/ bioactive constituents in dietary supplements (DS)

**Enhance database development**

- Focus Today

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**Notes:**
Our objective is to enhance database development, and that is our focus today. The ultimate goal, however, and the reason all of this is important is to better describe associations between dietary supplements and also total dietary intakes and health and disease outcomes. 

## Challenges in setting up a dietary supplement compositional database

**Categorizing product types in the database**
**Identifying nutrients/components of public health interest in these products**
**Quantifying those nutrients/components**

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## Challenges: DS Products, Components and Quantities  

| 
 |                                                                                     |  |  |
| --- | --- | --- | --- |
| Multivitamin Mineral Products | 25 mg | 100 mcgm | 15 mg |
|     MVM for seniors | 10 mg | 200 mcgm | 30 mg |
|     MVM for children | 2 mg | 2 mcgm | 2 mg |

**Components **

**	****Iron****	**

**Daidzein**

**Omega 3**

- quantity

- Products

- DSID

## Challenge #1

- Categorizing products in the database

**Notes:**
The best ways to categorize products in the database depends on the goal or purpose of the researcher. However there are some standardized ways of categorizing for foods, for example.

## Categorizing Products : Best ways to categorize products depends on purpose—one logical grouping

| 
 |  |  |  |
| --- | --- | --- | --- |
| Grain & grain products |  |  |  |
|     Bread |  |  |  |
|     Cereal |  |  |  |

- Products

- DSID

## Foods: Conventions accepted for categories

***Source/origin***
***Use in meals***** **
***Nutrients ***
***rich sources of nutrients***

- DSID

**Notes:**

Food category conventions exist, such as: 
By source/origin (Meat, Dairy, etc)
By use in meals (snacks, breakfast cereals)
By nutrients nutrient categories may be used to identify unique contributor sof nutrients, or rich sources of nutrients; (rich vit A foods or major sources of nutrients in diets as in lists of nutrient sources)

For  apractical application of food category conventions for grouping, even though many orange juices are now fortified with calcium, they are not cetegorized as dairy. 
Another convention used to categorize foods is food exchange lists that group different nutrients together are frequently used 

## Drug category conventions also exist

***Intended or end use or function: ***
***Chemical names***

- DSID

**Notes:**
Let’s take a look at drugs as well, since dietary supplements are somewhat like foods, and somewhat like drugs, and regulated in as foods but in ways that resemble both

Intended or end use or function: 
cholesterol lowering, diuretic, analgesic, etc.
HOWEVER, there are also off-label uses, or uses other than those intended such as antacids like TUMS being used as calcium supplements

Chemical content

## DS: Conventions not yet identified Many schemes possible

**Origin**
**Brand/manufacturer**
**End use**
**Chemical content**
**Market share**

- DSID

**Notes:**

There are many schemes that exist for categorizing dietary supplements, and conventions are not yet firmly established: For example, one can categorize by :

Origin:
 Nutrient type MVM, single nutrient/botanical
Brand
Centrum, Sundown, Sunup
End use
weight loss, joint health,  
Chemical
vitamins, minerals, etc
Market share
By shelf space in supermarket

## Categorizing Products: DS Database : 

|  |  |  |  |
| --- | --- | --- | --- |
| Multivitamin Mineral Products |  |  |  |
|     MVM for seniors |  |  |  |
|     MVM for children |  |  |  |

- Products

*One logical grouping*

- DSID

## Problems: DS Categorization 

**Today:** Myriad classifications used
- Different purposes
- Logic not always clear
- Categorization of convenience common
- Decisions subjective rather than objective
**Implications**
- Makes comparison between studies difficult
- Variability of nutrients within categories often great
- Categories often not
- Homogeneous
- mutually exclusive

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## Principles: Categorization of DS for Research Purposes

**Identify & standardize useful classification schemes for various uses**
**Explicit rationale/ logic & categorization criteria**
**Homogeneity**
**Mutually exclusive categories**

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**Notes:**
Thre are a number of principles that may be useful in developing categorization schemes for dietary supplements

Here are four general principles 
1. Identify several useful categorization schemes for various uses
but need to standardize them

2.State explicit rationale/ logic and criteria for categorization 

3.Strive for homogeneity
Amounts and types of key nutrients/ingredients within category need to be similar and need to be stated 

4.Strive for mutually exclusive categories
Many DS categories not mutually exclusive at present
Ex: MVM vs prenatal MVM with iron
Products to be grouped together and how must be determined? 

## Challenge #2

- Identify nutrients/ components of public health interest to put into the database

## Identify Nutritients/Bioactive Components: DS Database 

| 
 |                                                                                     |  |  |
| --- | --- | --- | --- |
| Multivitamin Mineral Products |  |  |  |
|     MVM for seniors |  |  |  |
|     MVM for children |  |  |  |

**Components **

**	****Iron****	**

**Daidzein**

**Omega 3**

- DSID

## Challenge 2: Identify and prioritize nutrients/components of greatest public health  interest

**Need list of nutrients/components of importance**
**Dietary supplements contain many nutrients/components **
**Can’t do all at once and interest only on some of these**
**Select most critical components –priority ranking**

- DSID

**Notes:**
We cannot have analytical values for everything
Time and money are limited

 There isnt enough time or money to have analytical values for everything. We need to prioritize the most important nutrients and components, and then select most critical components

## Basis for deciding on critical components

**Frequency of consumption (NHANES)**
**Public health significance (DRI nutrients so of known benefit, nutrient known to be short in diets, potential safety concerns)**
**Availability of methods and reference materials**
**Federal agency interest**

- DSID

## Dietary Supplement Ingredient Database   Priority List:

_**Phase 1**_
- Calcium, iron, magnesium, selenium, zinc
- Folate Vitamins A, B-carotene B6, B12, C, D, E
- Omega-3 fatty acids
- Potassium
- Sodium
- Iodine

_**Phase 2**_
- B1, B2, niacin, pantothenic acid, biotin
- Vitamin K
- Copper, chromium, manganese, molybdenum
- Phosphorus
- Lycopene, lutein, Ginkgo, isoflavones
- Caffeine

- DSID

## Challenge #3

- Quantifying priority nutrients/components

## Big Problem for Dietary Supplements

**Few publicly available chemically analyzed values for DS**
**NHANES database--only values declared on label available**

- DSID

**Notes:**
There is no Standard Reference volume, as there is for food composition tables for dietary supplements

In NHANES and other databases, unless specific laboratories or reasearchers have evaluated the supplements, such as Consumerlabs.com or researchers or clinicians, only values declared on the label are publicly available.

## Quantifying Nutritients/Bioactive Components in DS Database 

| 
 |                                                                                     |  |  |
| --- | --- | --- | --- |
| Multivitamin Mineral Products | 25 mg | 100 mcgm | 15 mg |
|     MVM for seniors | 10 mg | 200 mcgm | 30 mg |
|     MVM for children | 2 mg | 2 mcgm | 2 mg |

**Components **

- Products

**	****Iron****	**

**Daidzein**

**Omega 3**

- Analytical values needed

- DSID

## Challenge #3: Quantify priority nutrients/components

**Nutrients: *****straightforward****:*
**Active components known**
**Also in foods**
**Analytical methods often validated**
** ****although matrix varies, method can be validated**
**Benefits & public health importance known**

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## Saw 

**Saw **
**Palmetto**

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## Challenge #3: Quantify priority nutrients/components

**Botanicals: *****problematic***
**Active component largely unknown**
**Analytical methods not developed **
**Form not necessarily same as in foods**
**Efficacy often not established**
**Public health relevance unknown**

- DSID

**Notes:**
For botanicals, the active component is usually unknown, except for caffeine and a few others
The analytical methods are not developed, the form is not necessarilty the same as in foods, . 

Also the benefits may be perceived by users but are not neecessarily demonstrable objectively. 

And the public health relevance is often unknown.

## Ginkgo biloba

**Ginkgo biloba**

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## Challenge #3: Issues in quantifying priority nutrients/components

**Availability of analytical methods**
**Availability of reference materials**
**Necessary level of accuracy **
**Developing appropriate sampling plans**.

- DSID

## Availability of reference materials

**Problem:**
**Reference standards lacking to standardize chemical analysis of dietary supplements**
**Steps toward a Solution**:
**AOAC Methods validation**
**Develop standard reference materials (SRM) or certified reference materials (CRM) for dietary supplements  that labs can use**

- DSID

**Notes:**
The basic problem is that there are so many ingredients and so little time and money to accomplish all the tasks that are needed. ODS and government can only show the way to go, and cannot finish the job. Also for some dietary supplements, the active constituents are still unknown completely. 

## Standard Reference Materials (SRM )

**Cooperative agreement with National Institute of Standards and Technology (NIST) to prepare SRM **
**Multivitamin-mineral supplement**
**Ephedra, ginkgo, saw** **palmetto, St John’s wort, bitter orange, green tea, beta carotene, alpha tocoperol**
**Also NIST will update cod liver oil SRM to show individual fatty acids**

- DSID

## St. John’s 

**St. John’s **
**wort**

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## Needed analytical accuracy 

**Certain vitamins, minerals and other nutrients need high accuracy**
- Why: high public health import
- Ex   folic acid, calcium, D
- Need estimates of total dietary intake
**Botanicals: **depends on substance

- DSID

**Notes:**
One problem is that the needed analytical accuracy varies for each of the various dietary supplement ingredients. 

Nutrients : 
Estimates of total dietary intake needed
Fairly high degree of accuracy is needed  for nutrients of public health significance (Folic acid, calcium, D), but for others like choline less accuracy may be needed

Show n, mean, median and SD in database for individual items 
Acceptable variance permissible depends on significance of constituent in question

Botanicals :
Depends on substance
Caffeine , isoflavones
high degree of analytical accuracy may be needed 
Others 
Lycopene, etc: may only need rough amounts, such as label values  

For example, for nutrients, estimates of total dietary intake are needed, and a fairly high degree of accuracy is needed, especially for nutrients of public health significance, like folic acid, calcium and vitamin D. 

For botanicals, the analytical accuracy depends on the substance. For caffeine, or isoflavones, or ephedra, the degree of analytical accuracy may need to be high. For others, such as lycopene, only rough amounts may be needed.

## Developing appropriate sampling plans

- Sampling weighted by frequency of use
- Marketing sectors for products defined to begin process

- DSID

**Notes:**
The sampling plan is being developed in cooperation with the National Agricultural Statistics Service of the USDA to select reprsentative units of dietary supplement products. 

## DS Marketing Sectors

**Direct**
**Sales**

- DSID

**Notes:**
There are about 200 suppliers and perhaps 1000 growers, handlers, refiners and extractors who produce the raw materials for dietary supplements, especially the botanicals. There are about 890 companies that are manufacturers or processors. Then these are distributed in two major channels; retail sales (about 13,000 natural and health food stoes, 8,000 vitmin mineral supplement stores like GNC and others, 101,000 groceries and supermarkets, 42,000 druggists, 6,000 clubs and 65,000 convenience stores. With respect to the direct sales channel, about 1000 direct marketing companies exist, and there are 451,000 alternative medical practitioners who also sell dietary supplements.

On this slide the two direct sales bodies are shown, as well as the retail sales units. 

## Proposed ODS/ARS/USDA Pilot to test current labs ability to analyze VMS commonly consumed in NHANES 99-2000

**1 Methods for foods ok for DS?**
**2. Do labels reflect actual contents of the DS?**
**3. Variability between lots?**

- DSID

**Notes:**
1 Methods for foods ok for VMS ?
Different matrices: tablets, gel caps, chews

2. Do labels reflect actual VMS in the DS?
MVMs, antacids, E, C, Ca, B and B complex

3. Variability between lots????

## Progress toward analytically supported Dietary Supplement Data Base

- DSID

## Process

***We are***
*** ******here***

- DSID

**Notes:**
There are many other challenges: Why do people take dietary supplements?  What should a publicly available dietary supplement database look like? What is the most useful kind of information on ditary supplements to collect in federal surveys like the NHANES? And what is the best way to collect it. These are all important issues to deal with in the future. So there are many challenges left.!

**Visit the ODS home page**

- http://ods.od.nih.gov

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## Give us your views!

- DSID