Dietary Interventions for Osteoarthritis Pain

(DIRECTPain Trial)

Overseen By Amy M Goss, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Must not be taking: Opioids, Metabolism-altering, Anti-hypertensives

Disqualifiers: Diabetes, Eating disorders, Cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two diets to determine which better reduces knee pain from osteoarthritis (OA). One group will follow a low-carbohydrate diet, while the other will consume meals designed by the USDA (United States Department of Agriculture). Researchers aim to discover if these diets can relieve pain and improve daily life without medication. Adults who have experienced knee pain most days for the past three months and consume more than 100 grams of carbohydrates daily might be suitable for this study. Participants will receive all meals during the trial to ensure adherence to their assigned diets. As an unphased trial, this study provides a unique opportunity to explore dietary changes as a potential non-medication-based solution for knee pain relief.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you use daily opioid pain medications or medications that alter metabolism or digestion.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that a low-carbohydrate diet (LCD) is generally safe for people with knee osteoarthritis (OA). Studies have found that this diet can reduce knee pain without major side effects. One study noted that LCDs could lower pain levels, improving the quality of life for those with knee OA. Most people on this diet experienced only minor issues like temporary tiredness or headaches.

The USDA diet, which follows standard dietary guidelines, is also considered safe and beneficial. Research suggests that eating a balanced diet can lower the risk of developing knee OA. This diet focuses on a mix of nutrients that support overall health and may help with knee pain.

Both diets appear safe and well-tolerated, offering promising options for managing knee OA pain without medication. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these dietary interventions for osteoarthritis pain because they offer a potential non-drug alternative to traditional treatments like pain relievers and anti-inflammatory medications. Unlike standard options that often focus on symptom relief, a low-carbohydrate diet might address underlying inflammation by changing the body's metabolism. Meanwhile, the USDA diet aims to provide balanced nutrition, which could improve overall joint health and reduce pain. These dietary approaches could offer a safer, more sustainable way to manage osteoarthritis symptoms for adults aged 40-75.

What evidence suggests that this trial's dietary interventions could be effective for knee osteoarthritis pain?

This trial will compare the effects of a low-carbohydrate diet (LCD) and the USDA diet on knee osteoarthritis (OA) pain. Research has shown that LCDs can reduce pain in people with knee OA by lowering pain levels and improving quality of life, even without weight loss. This diet appears to work by reducing inflammation, a common cause of pain in OA. In contrast, the USDA diet, which is high in fiber, has been linked to a lower risk of developing OA. Fiber-rich diets might also alleviate symptoms by reducing inflammation. Both diets are being studied in this trial for their potential to reduce pain and improve well-being in those with knee OA, but the LCD might be more effective for pain relief. ^{1 2 6 7 8}

Who Is on the Research Team?

Robert E Sorge, PhD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for English-speaking adults aged 40-75 with knee osteoarthritis, who self-identify as either Non-Hispanic Black or White, have a BMI of 25-40, eat more than 100g of carbs daily, and experience pain most days. Excluded are those on opioids or certain other meds, with recent weight change, major surgery like knee replacement, severe diseases affecting heart/lungs/digestion/metabolism, extreme exercisers or dieters.

Inclusion Criteria

Average daily consumption of >100 g carbohydrates (based on Phase 1 food checklist)

BMI between 25 and 40 kg/m2

Self-identification as either NHB or NHW

Exclusion Criteria

I have lost or gained more than 4 kg in the last month.

I have not been hospitalized for an eating or psychiatric disorder in the last 6 months.

I have diabetes and am not taking medication for it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Participants undergo baseline assessments including anthropometric measures, actigraphy, and diet-related questionnaires

1 week

1 visit (in-person)

Diet Intervention

Participants are randomly assigned to either a Low-Carbohydrate Diet (LCD) or USDA diet, with weekly food delivery and monitoring

6 weeks

Weekly virtual check-ins

Follow-up

Participants are monitored for changes in pain, quality of life, and physiological measures after the intervention

3 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Low-carbohydrate diet
• USDA Diet

Trial Overview The study tests if a low-carbohydrate diet can reduce pain and improve quality of life in people with knee OA compared to the standard USDA diet. It will also look at how race might affect these outcomes by focusing on differences between Non-Hispanic Blacks and Whites.

How Is the Trial Designed?

Group I: USDA Diet Experimental Treatment 1 Intervention

Adults ages 40-75 with knee OA.

Group II: Low Carbohydrate Diet Experimental Treatment 1 Intervention

Adults ages 40-75 with knee OA.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

The Atkins diet, a high-fat ketogenic diet primarily consisting of animal products, can lead to health risks such as hyperlipidemia and hypercholesterolemia, even in children, due to its carbohydrate-free nature.

Given the potential hazards associated with the Atkins diet, including an increased risk of coronary heart disease, there is a significant concern about the safety of this dietary approach, highlighting the need for controlled studies to better understand its long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Is the Atkins diet safe in respect to health?]. Förster, H.[2006]

Participants on low carbohydrate high protein (LCHP) diets, the Zone diet, and conventional hypocaloric diets lost an average of 5.1 kg over 12 weeks, but there were no significant differences in weight or body fat loss among the different diet groups.

High attrition rates were observed across all diet plans, with 43% for LCHP, 60% for the Zone diet, and 36% for the conventional diet, indicating that adherence to these diets may be challenging for individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of weight loss plans on body composition and diet duration. Landers, P., Wolfe, MM., Glore, S., et al.[2006]

In a study of 5677 patients with type 2 diabetes over a median follow-up of 6.3 years, adherence to a healthy lower-carbohydrate diet was linked to a significantly lower risk of mortality, with the third quartile of overall diet score showing a 35% reduced risk compared to the lowest quartile.

Replacing just 2% of energy from carbohydrates with plant-based proteins or polyunsaturated fats was associated with a 23% to 37% reduction in total mortality, highlighting the importance of diet composition in managing long-term health outcomes for individuals with diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associations of Moderate Low-Carbohydrate Diets With Mortality Among Patients With Type 2 Diabetes: A Prospective Cohort Study. Wan, Z., Shan, Z., Geng, T., et al.[2022]

In a 3-month study involving 30 participants, those on a low-carbohydrate diet lost significantly more weight (6.39 kg) compared to controls (1.05 kg), indicating the diet's efficacy for weight loss.

Despite the weight loss, the low-carbohydrate diet did not lead to increased bone turnover markers compared to controls, suggesting that it may not negatively impact bone health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of a low-carbohydrate diet on bone turnover. Carter, JD., Vasey, FB., Valeriano, J.[2018]

The Active Low-Carber Forums (ALCF) study involved over 86,000 members, primarily women who were significantly overweight, with many successfully losing over 100 lbs using low carbohydrate diets, particularly the Atkins diet.

More than half of the respondents consulted a physician during their dieting journey, with many receiving support, indicating that low carbohydrate diets can be a viable recommendation for weight control and health improvement by family practitioners.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low carbohydrate diets in family practice: what can we learn from an internet-based support group. Feinman, RD., Vernon, MC., Westman, EC.[2018]

The Modified Atkins Diet (MAD) significantly improved seizure control in patients with intractable epilepsy, reducing daily seizure frequency from an average of 13.29 to 2.71 over nine months.

Mothers of the patients also experienced a significant improvement in their quality of life across all domains measured, indicating that MAD not only benefits the patients but also positively impacts their caregivers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with MAD on children with epilepsy in Egypt after classic KD failure. El Rashidy, OF., Nassar, MF., El Gendy, YG., et al.[2018]

High saturated fats, like those found in pork fat, and cholesterol significantly increase the risk of developing osteoarthritis in mice, while unsaturated fats, such as linoleic acid, can counteract these effects.

A high-protein diet may help prevent osteoarthritis in mice, but it can also lead to inflammation in humans, highlighting the complex relationship between diet and joint health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Potential effects of nutrition including additives on healthy and arthrotic joints. I. Basic dietary constituents]. Wilhelmi, G.[2006]

In a study of 89 obese patients with knee osteoarthritis, those on an intensive low-energy diet (LED) lost an average of 10.9 kg (11%) over one year, compared to a 3.6 kg (4%) loss in the control group, indicating significant weight loss efficacy (p<0.0001).

While both groups showed improvement in knee osteoarthritis symptoms, the LED group experienced a notable reduction in pain (7.2 mm difference on the WOMAC scale, p=0.022), suggesting that weight loss can lead to meaningful pain relief in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight loss as treatment for knee osteoarthritis symptoms in obese patients: 1-year results from a randomised controlled trial. Bliddal, H., Leeds, AR., Stigsgaard, L., et al.[2011]

In a study of 77 osteoarthritis patients over 12 weeks, 79% were found to be obese, which was linked to increased pain from osteoarthritis, indicating that weight management could be crucial for pain relief.

The patients had dietary deficiencies in key nutrients like vitamin D and zinc, suggesting that improving nutrition alongside weight loss could enhance their overall management of osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutrient intake and obesity in a multidisciplinary assessment of osteoarthritis. White-O'Connor, B., Sobal, J.[2013]

Low-carbohydrate (LC) diets have been shown to be as effective, or even more effective, than low-fat (LF) diets for weight loss and improving cardiovascular risk factors, based on both short-term and long-term studies.

The review suggests that LC diets can positively impact metabolic and hormonal responses, making them a viable alternative for managing obesity, diabetes, and heart disease risk in the American population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-carbohydrate diet review: shifting the paradigm. Hite, AH., Berkowitz, VG., Berkowitz, K.[2011]

In a study of 87 children on the modified Atkins diet for epilepsy, 55% of those who continued for over 6 months experienced more than a 50% improvement in seizures, and 35% became seizure-free after an average of 19.9 months.

The diet showed similar efficacy to short-term studies and long-term ketogenic diets, but side effects included increased lipid levels and gastrointestinal issues, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of children treated with the modified Atkins diet. Chen, W., Kossoff, EH.[2017]

In a study of 129 patients with knee osteoarthritis over 12 weeks, those following a Mediterranean diet experienced significantly greater reductions in pain compared to those on a low-fat or regular diet.

Both the Mediterranean and low-fat diets led to significant weight loss, but the Mediterranean diet was more effective in improving physical function and reducing pain severity, suggesting that its specific dietary components may play a crucial role in managing osteoarthritis symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a Mediterranean Diet Compared with the Low-Fat Diet on Patients with Knee Osteoarthritis: A Randomized Feeding Trial. Sadeghi, A., Zarrinjooiee, G., Mousavi, SN., et al.[2022]

In a study of 21,901 American adults, higher adherence to the DASH dietary pattern was linked to a lower likelihood of having osteoarthritis (OA), with a significant trend observed across different levels of adherence.

The results suggest that following the DASH diet, which emphasizes fruits, vegetables, and whole grains, may help reduce the risk of developing OA among older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence to DASH dietary pattern is inversely associated with osteoarthritis in Americans. Zhang, Y., Francis, EC., Xia, T., et al.[2021]

The modified Atkins diet (MAD) effectively reduced seizures in approximately 50% of children with intractable epilepsy and metabolic conditions over a 24-month period.

Importantly, the MAD did not negatively impact growth or bone mass in children, indicating it is a safe long-term treatment option compared to more restrictive diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective study of growth and bone mass in Swedish children treated with the modified Atkins diet. Svedlund, A., Hallböök, T., Magnusson, P., et al.[2019]

Citations

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The effect of a low-carbohydrate diet on evoked pain and ... In addition, we have shown that a low-carbohydrate diet (LCD), but not a low-fat diet, can reduce pain in adults with chronic KOA [43].

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11479182/

Efficacy, Safety, and Tolerability of a Very Low-Calorie ... Preliminary results suggest that a low-carbohydrate diet may alleviate pain in patients with knee OA, independent of weight loss, although specific evidence ...

3. nature.com nature.com/articles/s41430-025-01622-0

The effectiveness of dietary intervention in osteoarthritis ... Our research indicates that dietary interventions are effective in alleviating pain among patients with OA, with reduced energy diets showing ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7999621/

The Effect of Low-Carbohydrate and Low-Fat Diets on Pain in ... Diets such as the Mediterranean diet (a partial low-carbohydrate diet) have been shown to reduce inflammation in arthritis patients [15] and ...

5. uab.edu uab.edu/news/health-medicine/study-low-carb-diet-provides-relief-from-knee-osteoarthritis

Study: Low-carb diet provides relief from knee osteoarthritis A study conducted at the University of Alabama at Birmingham shows a low-carbohydrate diet was more effective in reducing pain intensity than a low-fat diet.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39702235/

The effect of a low-carbohydrate diet on evoked pain and ... We have shown that a low-carbohydrate diet (LCD) can reduce KOA-related pain. Our previous work suggested that the LCD was more beneficial for ...

7. frontiersin.org frontiersin.org/journals/nutrition/articles/10.3389/fnut.2021.702802/full

Ketogenic Diets and Chronic Disease: Weighing the ... This review examines the effects of ketogenic diets on common chronic diseases, as well as their impact on diet quality and possible risks associated with ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2451847623000209

Effect of low-calorie ketogenic vs low-carbohydrate diets on ... This study investigated the effects of a low-calorie ketogenic diet (LCKD) (10–15% carbohydrate, 60–75% fat, 10–25% protein) compared with a low-carbohydrate ...